EGFR/Ras/MAPK Signaling Mediates Adult Midgut Epithelial Homeostasis and Regeneration in Drosophila

SummaryMany tissues in higher animals undergo dynamic homeostatic growth, wherein damaged or aged cells are replaced by the progeny of resident stem cells. To maintain homeostasis, stem cells must respond to tissue needs. Here we show that in response to damage or stress in the intestinal (midgut) epithelium of adult Drosophila, multiple EGFR ligands and rhomboids (intramembrane proteases that activate some EGFR ligands) are induced, leading to the activation of EGFR signaling in intestinal stem cells (ISCs). Activation of EGFR signaling promotes ISC division and midgut epithelium regeneration, thereby maintaining tissue homeostasis. ISCs defective in EGFR signaling cannot grow or divide, are poorly maintained, and cannot support midgut epithelium regeneration after enteric infection by the bacterium Pseudomonas entomophila. Furthermore, ISC proliferation induced by Jak/Stat signaling is dependent upon EGFR signaling. Thus the EGFR/Ras/MAPK signaling pathway plays central, essential roles in ISC maintenance and the feedback system that mediates intestinal homeostasis.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (405 K)Download as PowerPoint slideHighlights► EGFR/MAPK signaling controls homeostasis and regeneration in the Drosophila midgut ► Within the niche, different cell types secrete EGFR ligands in response to stress ► EGFR activity is required and sufficient to promote intestinal stem cell division ► EGFR and Jak/Stat signaling act in synergy to induce ISC proliferation